I am creating a PDF in illustrator, then I save it, and use Acrobat (Crop Pages) to add margins, including center + 1/2" margin all around. It's worked for me just fine for multiple files. But this one 30-page file... I do everything like normal, but one page (the first page) will uncenter every time I save the file, and align to left and bottom instead of the 1/2" margins on all sides. It's ONLY when I save the file. I've tried different computers. It's just this file and this page and I have no idea why, it's pretty much the same as the other pages!

I thought the same thing! So I created a new artboard and just dragged my content over to the new one, same thing! It's so bizarre. And the content on that page is basically text and vector copied from other files that worked just fine!

I tried the steps you outlined (create a 7.5x10" document in Illustrator, assemble multiple of these documents in Acrobat, then try to enlarge the page size to 8.5x11"), but I cannot re-create what you see. I can see from your screenshots that it's happening on your system, but without access to the actual PDF file, it may be impossible to say what's going on.